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Dual frequency magnetic excitation of magnetic nanoparticles (MNP) enables enhanced biosensing applications. This was studied from an experimental and theoretical perspective: nonlinear sum-frequency components of MNP exposed to dual-frequency magnetic excitation were measured as a function of static magnetic offset field. The Langevin model in thermodynamic equilibrium was fitted to the experimental data to derive parameters of the lognormal core size distribution. These parameters were subsequently used as inputs for micromagnetic Monte-Carlo (MC)-simulations. From the hysteresis loops obtained from MC-simulations, sum-frequency components were numerically demodulated and compared with both experiment and Langevin model predictions. From the latter, we derived that approximately 90% of the frequency mixing magnetic response signal is generated by the largest 10% of MNP. We therefore suggest that small particles do not contribute to the frequency mixing signal, which is supported by MC-simulation results. Both theoretical approaches describe the experimental signal shapes well, but with notable differences between experiment and micromagnetic simulations. These deviations could result from Brownian relaxations which are, albeit experimentally inhibited, included in MC-simulation, or (yet unconsidered) cluster-effects of MNP, or inaccurately derived input for MC-simulations, because the largest particles dominate the experimental signal but concurrently do not fulfill the precondition of thermodynamic equilibrium required by Langevin theory.
Magnetic nanoparticle relaxation in biomedical application: focus on simulating nanoparticle heating
(2021)
Frequency mixing magnetic detection (FMMD) is a sensitive and selective technique to detect magnetic nanoparticles (MNPs) serving as probes for binding biological targets. Its principle relies on the nonlinear magnetic relaxation dynamics of a particle ensemble interacting with a dual frequency external magnetic field. In order to increase its sensitivity, lower its limit of detection and overall improve its applicability in biosensing, matching combinations of external field parameters and internal particle properties are being sought to advance FMMD. In this study, we systematically probe the aforementioned interaction with coupled Néel–Brownian dynamic relaxation simulations to examine how key MNP properties as well as applied field parameters affect the frequency mixing signal generation. It is found that the core size of MNPs dominates their nonlinear magnetic response, with the strongest contributions from the largest particles. The drive field amplitude dominates the shape of the field-dependent response, whereas effective anisotropy and hydrodynamic size of the particles only weakly influence the signal generation in FMMD. For tailoring the MNP properties and parameters of the setup towards optimal FMMD signal generation, our findings suggest choosing large particles of core sizes dc > 25 nm nm with narrow size distributions (σ < 0.1) to minimize the required drive field amplitude. This allows potential improvements of FMMD as a stand-alone application, as well as advances in magnetic particle imaging, hyperthermia and magnetic immunoassays.
The hybrid K+/Ca2+ sensor based on laser scanned silicon transducer for multi-component analysis
(2002)
Purpose — to compare the chemical elemental composition of vitreous cavity content taken from cadaveric eyes compared to samples taken from the eyes with terminal stage refractory glaucoma with decompensated intraocular pressure (IOP). Material and methods. The vitreous contents of the eyes from 2 groups were studied. The 1st group included 15 cadaveric eyes; the 2nd group included 15 eyes with refractory glaucoma in the terminal stage of the disease with decompensated IOP in patients with hypertension pain. The vitreal content samples were taken in the course of antiglaucoma surgery aimed at preserving the eye as an organ and involving employment of drainage in the vitreous cavity. The study of virtual contents was carried out on energy dispersive spectrometer Oxford X-Max 50 integrated into scanning electron microscope Zeiss EVO LS10. Results. Increased concentrations of Kalium and Phosphorus were detected in the vitreous content of cadaveric eyes compared with the vitreal content from the eyes with terminal glaucoma with decompensated IOP taken in vivo (K — 0.172/0.093; P — 0.045/0.025 mmol/L). In the vitreous cavity in the eyes with end-stage glaucoma with decompensated IOP, the concentration of Nitrogen was higher in comparison with human cadaver eyes (2.030/1.424 mmol/L). Conclusion. The increased concentrations of Kalium and Phosphorus in the vitreous content of cadaveric eyes is associated with postmortem autolytic processes and with the release of intracellular content in the destruction of cell membranes. The increased Nitrogen concentration in the vitreal contents of the eyes with terminal stage glaucoma with decompensated IOP may be associated with the presence of osmotically active nitrogen-containing compounds in the eyes with increased IOP.
Optimization of passivation layers for corrosion protection of silicon-based microelectrode arrays
(2000)
Malaria infection remains a significant risk for much of the population of tropical and subtropical areas, particularly in developing countries. Therefore, it is of high importance to develop sensitive, accurate and inexpensive malaria diagnosis tests. Here, we present a novel aptamer-based electrochemical biosensor (aptasensor) for malaria detection by impedance spectroscopy, through the specific recognition between a highly discriminatory DNA aptamer and its target Plasmodium falciparum lactate dehydrogenase (PfLDH). Interestingly, due to the isoelectric point (pI) of PfLDH, the aptasensor response showed an adjustable detection range based on the different protein net-charge at variable pH environments. The specific aptamer recognition allows sensitive protein detection with an expanded detection range and a low detection limit, as well as a high specificity for PfLDH compared to analogous proteins. The specific feasibility of the aptasensor is further demonstrated by detection of the target PfLDH in human serum. Furthermore, the aptasensor can be easily regenerated and thus applied for multiple usages. The robustness, sensitivity, and reusability of the presented aptasensor make it a promising candidate for point-of-care diagnostic systems.
We present an electromechanically coupled Finite Element model for cardiac tissue. It bases on the mechanical model for cardiac tissue of Hunter et al. that we couple to the McAllister-Noble-Tsien electrophysiological model of purkinje fibre cells. The corresponding system of ordinary differential equations is implemented on the level of the constitutive equations in a geometrically and physically nonlinear version of the so-called edge-based smoothed FEM for plates. Mechanical material parameters are determined from our own pressure-deflection experimental setup. The main purpose of the model is to further examine the experimental results not only on mechanical but also on electrophysiological level down to ion channel gates. Moreover, we present first drug treatment simulations and validate the model with respect to the experiments.
We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures.
Effectiveness of the edge-based smoothed finite element method applied to soft biological tissues
(2012)
Two single-incision mini-slings used for treating urinary incontinence in women are compared with respect to the stresses they produce in their surrounding tissue. In an earlier paper we experimentally observed that these implants produce considerably different stress distributions in a muscle tissue equivalent. Here we perform 2D finite element analyses to compare the shear stresses and normal stresses in the tissue equivalent for the two meshes and to investigate their failure behavior. The results clearly show that the Gynecare TVT fails for increasing loads in a zipper-like manner because it gradually debonds from the surrounding tissue. Contrary to that, the tissue at the ends of the DynaMesh-SIS direct may rupture but only at higher loads. The simulation results are in good agreement with the experimental observations thus the computational model helps to interpret the experimental results and provides a tool for qualitative evaluation of mesh implants.
Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) today are widely used for the investigation of normal electromechanical cardiac function, of cardiac medication and of mutations. Computational models are thus established that simulate the behavior of this kind of cells. This section first motivates the modeling of hiPS-CM and then presents and discusses several modeling approaches of microscopic and macroscopic constituents of human-induced pluripotent stem cell-derived and mature human cardiac tissue. The focus is led on the mapping of the computational results one can achieve with these models onto mature human cardiomyocyte models, the latter being the real matter of interest. Model adaptivity is the key feature that is discussed because it opens the way for modeling various biological effects like biological variability, medication, mutation and phenotypical expression. We compare the computational with experimental results with respect to normal cardiac function and with respect to inotropic and chronotropic drug effects. The section closes with a discussion on the status quo of the specificity of computational models and on what challenges have to be solved to reach patient-specificity.
GaAs-based Gunn diodes with graded AlGaAs hot electron injector heterostructures have been developed under the special needs in automotive applications. The fabrication of the Gunn diode chips was based on total substrate removal and processing of integrated Au heat sinks. Especially, the thermal and RF behavior of the diodes have been analyzed by DC, impedance and S-parameter measurements. The electrical investigations have revealed the functionality of the hot electron injector. An optimized layer structure could fulfill the requirements in adaptive cruise control (ACC) systems at 77 GHz with typical output power between 50 and 90 mW.
Es werden Effizienzbegriffe zum Vergleich von statistischen Tests basierend auf verschiedenen statistischen Experimenten eingeführt. Dabei handelt es sich um die schon aus dem Vergleich von statistischen Tests in je demselben Modell bekannten asymptotischen relativen Effizienzen wie die Hodges-Lehmann-Effizienz, die Bahadur-Effizienz und die Pitman-Effizienz sowie um Kriterien basierend auf Volumina von Konfidenzbereichen. Effizienzaussagen werden unter anderem für Likelihood-Quotienten-Tests und Waldsche Tests im Rahmen eines allgemeinen multivariaten parametrischen Modells erhalten. Statistische Tests zur Prüfung von Hypothesen über die relative Wirksamkeit zweier Experimente werden vorgeschlagen. Auf der Grundlage der erhaltenen Ergebnisse erfolgt ein Vergleich der Wirksamkeit von korrespondierenden Verfahren bei verbundener Stichprobenerhebung und unabhängiger Stichprobenerhebung. Die Rolle der Kovarianzmatrix bei verbundener Stichprobenerhebung wird insbesondere unter der Annahme, dass die zugrunde liegenden Verteilungen durch k-parametrische Exponentialfamilien modellierbar sind, herausgearbeitet. Verbindungen zu Effizienzbegriffen bei Punkt- und Konfidenzbereichsschätzverfahren werden aufgezeigt. Ausführlichere Untersuchungen betreffen die korrespondierenden Hotellingschen T²-Tests im multivariaten Normalverteilungsfall, die klassischen Homogenitatstests bei k × k-Kontingenztafeln und die Wilcoxon Tests in nichtparametrischen Lagealternativmodellen
Selected problems in the field of multivariate statistical analysis are treated. Thereby, one focus is on the paired sample case. Among other things, statistical testing problems of marginal homogeneity are under consideration. In detail, properties of Hotelling‘s T² test in a special parametric situation are obtained. Moreover, the nonparametric problem of marginal homogeneity is discussed on the basis of possibly incomplete data. In the bivariate data case, properties of the Hoeffding-Blum-Kiefer-Rosenblatt independence test statistic on the basis of partly not identically distributed data are investigated. Similar testing problems are treated within the scope of the application of a result for the empirical process of the concomitants for partly categorial data. Furthermore, testing changes in the modeled solvency capital requirement of an insurance company by means of a paired sample from an internal risk model is discussed. Beyond the paired sample case, a new asymptotic relative efficiency concept based on the expected volumes of multidimensional confidence regions is introduced. Besides, a new approach for the treatment of the multi-sample goodness-of-fit problem is presented. Finally, a consistent test for the treatment of the goodness-of-fit problem is developed for the background of huge or infinite dimensional data.
We consider time-dependent portfolios and discuss the allocation of changes in the risk of a portfolio to changes in the portfolio’s components. For this purpose we adopt established allocation principles. We also use our approach to obtain forecasts for changes in the risk of the portfolio’s components. To put the approach into practice we present an implementation based on the output of a simulation. Allocation is illustrated with an example portfolio in the context of Solvency II. The quality of the forecasts is investigated with an empirical study.
On the applicability of several tests to models with not identically distributed random effects
(2023)
We consider Kolmogorov–Smirnov and Cramér–von-Mises type tests for testing central symmetry, exchangeability, and independence. In the standard case, the tests are intended for the application to independent and identically distributed data with unknown distribution. The tests are available for multivariate data and bootstrap procedures are suitable to obtain critical values. We discuss the applicability of the tests to random effects models, where the random effects are independent but not necessarily identically distributed and with possibly unknown distributions. Theoretical results show the adequacy of the tests in this situation. The quality of the tests in models with random effects is investigated by simulations. Empirical results obtained confirm the theoretical findings. A real data example illustrates the application.
The Rothman–Woodroofe symmetry test statistic is revisited on the basis of independent but not necessarily identically distributed random variables. The distribution-freeness if the underlying distributions are all symmetric and continuous is obtained. The results are applied for testing symmetry in a meta-analysis random effects model. The consistency of the procedure is discussed in this situation as well. A comparison with an alternative proposal from the literature is conducted via simulations. Real data are analyzed to demonstrate how the new approach works in practice.
In the context of the Solvency II directive, the operation of an internal risk model is a possible way for risk assessment and for the determination of the solvency capital requirement of an insurance company in the European Union. A Monte Carlo procedure is customary to generate a model output. To be compliant with the directive, validation of the internal risk model is conducted on the basis of the model output. For this purpose, we suggest a new test for checking whether there is a significant change in the modeled solvency capital requirement. Asymptotic properties of the test statistic are investigated and a bootstrap approximation is justified. A simulation study investigates the performance of the test in the finite sample case and confirms the theoretical results. The internal risk model and the application of the test is illustrated in a simplified example. The method has more general usage for inference of a broad class of law-invariant and coherent risk measures on the basis of a paired sample.
We discuss the testing problem of homogeneity of the marginal distributions of a continuous bivariate distribution based on a paired sample with possibly missing components (missing completely at random). Applying the well-known two-sample Crámer–von-Mises distance to the remaining data, we determine the limiting null distribution of our test statistic in this situation. It is seen that a new resampling approach is appropriate for the approximation of the unknown null distribution. We prove that the resulting test asymptotically reaches the significance level and is consistent. Properties of the test under local alternatives are pointed out as well. Simulations investigate the quality of the approximation and the power of the new approach in the finite sample case. As an illustration we apply the test to real data sets.
Suppose we have k samples X₁,₁,…,X₁,ₙ₁,…,Xₖ,₁,…,Xₖ,ₙₖ with different sample sizes ₙ₁,…,ₙₖ and unknown underlying distribution functions F₁,…,Fₖ as observations plus k families of distribution functions {G₁(⋅,ϑ);ϑ∈Θ},…,{Gₖ(⋅,ϑ);ϑ∈Θ}, each indexed by elements ϑ from the same parameter set Θ, we consider the new goodness-of-fit problem whether or not (F₁,…,Fₖ) belongs to the parametric family {(G₁(⋅,ϑ),…,Gₖ(⋅,ϑ));ϑ∈Θ}. New test statistics are presented and a parametric bootstrap procedure for the approximation of the unknown null distributions is discussed. Under regularity assumptions, it is proved that the approximation works asymptotically, and the limiting distributions of the test statistics in the null hypothesis case are determined. Simulation studies investigate the quality of the new approach for small and moderate sample sizes. Applications to real-data sets illustrate how the idea can be used for verifying model assumptions.